Although considerable work has been performed recently on the clinical and biological features of the cognitive impairment of AD, little attention has been paid to the psychiatric symptoms. In the proposed University Hospitals of Cleveland/Case Western Reserve University (UHC/CWRU) Alzheimer Clinical Research Center (ACRC), we will characterize cognitive and psychiatric symptoms of a population of AD patients, follow them longitudinally, and explore the relationships between alterations in adrenergic and serotonergic markers in life and in death with the clinical features. The goal of this ACRC is to contribute to a better understanding of the biological basis of the cognitive and behavioral manifestations of AD, which will lead to better diagnostic and therapeutic approaches. This goal will be accomplished through six cores: Clinical, Clinical Pharmacology Neuroimaging, Neuropathology, Data Management and Analysis, and Administrative. The cores will serve as a resource for investigators in the ACRC, as well as other investigators at UHC/CWRU. A comprehensive diagnostic and therapeutic approach to the cognitive and psychiatric manifestations of AD obviously requires both biological and behavioral aspects. Five specific research projects are included in the proposal: 1) biochemical assessment of serotonergic and noradrenergic markers in blood platelets, 2) the role of adrenergic and serotonergic systems in the regulation of cortisol secretion and glucocorticoid receptor number, 3) post mortem alterations in cortical, adrenergic, and serotonergic binding sites, 4) description of the pathology of the locus coeruleus and raphe nucleii, and 5) studies of the neural control of blood-brain barrier regulation. In addition, mechanisms are specifically included in the ACRC to evaluate new research proposals generated by UHC/CWRU investigators.